The purpose of this project is to elucidate the interrelationship between anticancer activity and conformational preference of selected alkylating agents; consideration is also given to several aspects of chemical stability. Under current investigation are the P-N alkylating agents, cyclophosphamide and thiotepa, and their derivatives. The stability and conformational behavior of these agents are being probed by high-resolution NMR spectroscopy and molecular orbital calculations. It is hoped that insights gained through these studies will aid in the design of improved anti-tumor agents.